Data
continues to accumulate linking HIV infection itself and use of antiretroviral
therapy with increased risk of cardiovascular disease, as demonstrated by 2 recently
published studies.
Elevated
Risk of Heart Attack
In
the April 24, 2007 advance online edition of the Journal of
Clinical Endocrinology and Metabolism, Steven Grinspoon, MD, of Massachusetts
General Hospital (MGH) and colleagues reported data from a study looking at the
incidence of and risk factors for acute myocardial
infarction (heart attack) among people with HIV.
The
authors conducted a cohort study based on the large Research Patient Data Registry,
which included 3851 HIV positive patients (about 30% women; 24% African-American)
and 1,044,589 HIV negative individuals (about 60% women; 7% African-American)
receiving care at MGH and Brigham and Women's Hospital in Boston between October
1996 and June 2004; subjects were followed for a mean of about 4 years. Most of
the HIV positive patients were receiving HAART.
Results
·Acute myocardial
infarction was identified in 189 HIV positive and 26,142 HIV negative subjects.
·Acute myocardial
infarction rates were significantly higher in HIV positive compared with HIV negative patients (11.13 vs 6.98
cases per 1000 person-years).
·HIV positive
men and women were significantly more likely than HIV negative subjects to have
hypertension (21.2% vs 15.9%), diabetes (11.5% vs 6.6%), and dyslipidemia (23.3%
vs 17.6%) (all P < 0.0001).
·After adjusting
for age, sex, race, hypertension, diabetes, and dyslipidemia, HIV positive individuals
were nearly twice as likely to experience acute myocardial infarction (relative
risk 1.75; P < 0.0001).
·In the HIV
positive group, abnormal lipid levels (relative risk 3.65) and being African-American
(relative risk 1.43) were the only significant independent risk factors for myocardial
infarction.
·When men
and women were analyzed separately, unadjusted acute myocardial infarction rates
were significantly higher for HIV positive compared
with HIV negative women (12.71 vs 4.88 cases per 1000 person-years).
·However,
the difference in unadjusted rates between HIV positive and HIV negative men was
not statistically significant (10.48 vs 11.44 cases per 1000 person-years).
·After adjusting
for age, sex, race, hypertension, diabetes, and dyslipidemia, the relative risks
of acute myocardial infarction rates were 2.98 for women (i.e., nearly triple
the risk) (P < 0.0001) and 1.40 for men (P = 0.0003).
Conclusion
“Acute
myocardial infarction rates and cardiovascularrisk factors were increased
in HIV compared to non-HIV patients,particularly among women,” the authors concluded. “Cardiac risk modification
strategiesare important for the long-term care of HIV patients.”
They
noted that a limitation of this study is that the database did contain complete data on patients’ tobacco smoking habits (recorded
for only about one-quarter of subjects), which is a known risk factor for heart
disease.
In
their discussion, the researchers said that elevated blood lipids related to antiretroviral
therapy may contribute to the higher rate of myocardial infarction in people with
HIV. The reason for the higher risk in women is unclear, but they suggested that
body composition changes may play a role.
“Determining the mechanisms of increased cardiovascular
disease and cardiac risk factor rates in HIV-infected women is an important area
of future research,” they wrote.
Massachusetts
General Hospital Program in Nutritional Metabolism; MGHBiostatisticsCenter;
Brigham and Women's Hospital; HarvardMedicalSchool,
Boston, MA.
Role
of Protease Inhibitors
In
the second study, published in the April 26, 2007 New England Journal of Medicine,
an international team of researchers reported the latest data from the ongoing
D:A:D study.
As
background, the authors noted that they previously observed an association betweencombination antiretroviral therapy and risk of myocardialinfarction, but it is not yet clear whether this association differsaccording to class of antiretroviral drugs.
In
the present study, they investigate the link between myocardial infarction and
cumulative exposureto protease inhibitors (PIs) and non-nucleoside
reverse transcriptaseinhibitors (NNRTIs).
The
D:A:D cohort includes 23,437 HIV positive patients, mostly in European countries.
The researchers analyzed data collected through February 2005. Incidence rates
ofmyocardial infarction during the follow-up period were calculated,and associations with exposureto PIs and/or NNRTIs were determined.
Results
·345 patients
had a myocardial infarctionduring 94,469 person-years of observation.
·The incidence
ofmyocardial infarction increased from 1.53 per 1000 person-yearsin patients not exposed to PIs to 6.01 per 1000person-years
in those who received PIs for morethan 6 years.
·After adjusting
for exposure to the other drugclass and known cardiovascular risk
factors (excludinglipid levels), the relative risk of myocardial infarction
peryear of PI exposure was 1.16.
·The relative
risk peryear of exposure to NNRTIs was lower, at 1.05.
·Adjusting
for serum lipidlevels reduced the effect of PI exposure to a relative
risk of 1.10 and NNRTI exposure to a relative risk of 1.00 (i.e., no increased
risk).
Conclusion
“Increased
exposure to protease inhibitors is associatedwith an increased risk
of myocardial infarction, which is partlyexplained by dyslipidemia,”
the authors wrote. “We found no evidence of such an associationfor
non-nucleoside reverse-transcriptase inhibitors; however,the number
of person-years of observation for exposure to thisclass of drug was
less than that for exposure to protease inhibitors.”
In
an accompanying editorial, James Stein,
MD, of the University of Wisconsin School of Medicine and Public Health emphasized
that the magnitude of the increased risk of heart attack associated with protease
inhibitor use was low, especially compared with other known cardiovascular risk factors.
“Given the much greater cardiovascular risks associated
with diabetes mellitus and with smoking (and the high prevalence of smoking among
HIV-infected patients),” he suggested, “perhaps more effort should be spent assisting
our patients with smoking cessation and the prevention of diabetes, rather than
our focusing so intently on the dyslipidemic effects of antiretroviral therapy,
especially since uncontrolled viremia is a greater risk factor for death from
cardiovascular causes than are the metabolic changes associated with such therapy.”
“Patients with HIV infection are living longer -- that's
the good news,” he continued. “But the longer you live, the more likely it is
that heart disease will develop, so the treatment of modifiable risk factors is
prudent.
University
of Copenhagen, Copenhagen, Denmark; Academic Medical Center, Amsterdam, Netherlands;
Royal Free and University College, London, UK; University Hospital Zurich, Zurich,
Switzerland; University of Milan, Italy; Columbia University, Harlem Hospital,
New York, NY; INSERM E0338 and U593, Victor Segalen-Bordeaux 2 University, Bordeaux,
France; Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium; Centre
Hospitalier Universitaire, Hôpital de l'Archet, Nice, France; National Centre
for HIV Epidemiology and Clinical Research, Sydney, Australia.
05/01/07
References
VA
Triant, H Lee, C Hadigan, and others. Increased Acute Myocardial Infarction Rates
and Cardiovascular Risk Factors Among Patients with HIV Disease. J Clin Endocrinol Metab. April 24, 2007 [Epub ahead of print]
N
Friis-Møller, P Reiss, CA Sabin, and others (D:A:D Study Group). Class of Antiretroviral
Drugs and the Risk of Myocardial Infarction. New England Journal of Medicine
356(17): 1723-1735. April 26, 2007.
JH
Stein. Cardiovascular Risks of Antiretroviral Therapy. New England Journal
of Medicine 356(17): 1773-1775. April 26, 2007.
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